1. Field of the Invention
The present invention relates to a method of producing a 2-naphthamide derivative that can be employed as an antiallergic agent or an agent for curing allergosis, and also to compounds for producing the 2-naphthamide derivative.
2. Discussion of Background
Conventionally, a 3-hydroxy-2-naphthamide derivative is produced, for example, by any of the following three methods, as disclosed in U.S. Pat. No. 5,324,728:
(1) the hydroxyl group at position 3 of the 3-hydroxy-2-naphthoic acid derivative is protected with an acyl group. The carboxyl group of the thus protected 3-hydroxy-2-naphthoic acid derivative is then chlorinated, for example, by thionyl chloride, to obtain a protected 3-hydroxy-2-naphthoic acid chloride derivative. The thus obtained protected 3-hydroxy-2-naphthoic acid chloride derivative is then allowed to react with an amine compound to obtain a protected 3-hydroxy-2-naphthamide derivative. However, according to this method, it is necessary to remove the acyl group employed for the above-mentioned protection of the hydroxyl group. PA1 (2) A 3-hydroxy-2-naphthoic acid derivative is allowed to react with a carbodiimide reagent to produce a carbodiimide-reagent adduct. This adduct is then allowed to react with an amine compound. PA1 (3) The first mentioned protected 3-hydroxy-2-naphthoic acid chloride derivative or the above-mentioned carbodiimide-reagent adduct is allowed to react with an alcohol compound such as a nitrophenol compound or N-hydroxysuccinimide compound to obtain an active ester compound. The thus obtained active ester compound is then allowed to react with an amine compound. PA1 allowing a compound of formula (VI), ##STR5## wherein R.sup.1 is the same as defined in formula (I), and R.sup.4 is an unsubstituted or substituted alkyl group having 1 to 6 carbon atoms, to react with an aminoethylpiperidine derivative of formula (III), ##STR6## wherein R.sup.1 and R.sup.2 are respectively the same as defined in formula (I). PA1 wherein R.sup.3 is the same an defined in formula (I). PA1 allowing an acid anhydride derivative of formula (VII), ##STR8## wherein R.sup.3 is the same as defined in formula (I), and R.sup.5 an unsubstituted or substituted alkyl group having 1 to 5 carbon atoms; R.sup.6 is a hydrogen atom, or ##STR9## to react with an aminoethylpiperidine derivative of formula (III), ##STR10## wherein R.sup.1 and R.sup.2 are respectively the same as defined in formula (I), to produce a reaction product corresponding to said 2-naphthamide derivative of formula (I), with the hydrolysis of the reaction product only when R.sup.6 is ##STR11## PA1 allowing a naphthoic acid derivative of formula (VIII), ##STR12## wherein R.sup.4 is the same as defined in formula (I), to react with an acyl derivative of formula (IX), EQU R.sup.5 COX.sup.1 (IX) PA1 allowing a dihydroxynaphthoic acid ester derivative of formula (IV), ##STR23## wherein R.sup.4 is an unsubstituted or substituted alkyl group having 1 to 6 carbon atoms, to react with an alcohol derivative of formula (V), EQU R.sup.3 --OH (V) PA1 wherein R.sup.3 is the same as defined in formula (I), to obtain a compound of formula (VI), ##STR24## wherein R.sup.3 is the same as defined in formula (I), and R.sup.4 is the same as defined in formula (IV), and PA1 allowing the compound of formula (VI) to react with an aminoethylpiparidine derivative of formula (III), ##STR25## wherein R.sup.1 and R.sup.2 are respectively the same as defined in formula (I). PA1 wherein R.sup.5 is an unsubstituted or substituted alkyl group having 1 to 5 carbon atoms; and X.sup.1 is a halogen atom such as chlorine, bromine and iodine, to prepare an acid anhydride derivative of formula (VII), ##STR34## wherein R.sup.3 is the same as defined in formula (I), and R.sup.5 and R.sup.6 are respectively the same as defined in formula (VIII).
The first method (1), however, has the shortcomings that a step of protecting the hydroxyl group is required and that much by-products are produced since the reactions are carried out via unstable intermediates.
The second method (2) has the shortcomings that not only an expensive carbodiimide agent is required, but also, there must be conducted a difficult purification step for removing urea which is produced in a large amount in the reaction mixture.
The third method (3) has the shortcomings that complicated production stops are involved since after the protected 3-hydroxy-2-naphthoic acid chloride derivative or the carbodiimide-reagent adduct is produced, an alcohol compound has to be reacted therewith.
Thus, the above-mentioned 3-hydroxy-2-naphthamide derivative cannot be produced easily and with high yield by the conventional methods, and therefore such conventional methods are unsatisfactory as an industrially applicable method for producing the 3-hydroxy-2-naphthamide derivative.